Additional file 1: of Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers

Table S1. Genomic regions showing copy number loss or loss/LOH in at least 70% of ATM-associated tumours. (XLSX 70 kb

Additional file 3: of Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers

Table S2. Comparison of genes altered at the copy number level between ATM-associated tumours and tumours from TCGA. (XLSX 13 kb

Mapping of the 17q21 locus.

<p><i>Top 3 panels:</i> P-values of association (−log₁₀ scale) with ovarian cancer risk for genotyped and imputed SNPs (1000 Genomes Project CEU), by chromosome position (b.37) at the 17q21 region, for <i>BRCA1</i>, <i>BRCA2</i> mutation carriers and combined. Results based on the kinship-adjusted score test statistic (1 d.f.). <i>Fourth panel:</i> Genes in the region spanning (43.4–44.9 Mb, b.37) and the location of the most significant genotyped SNPs (in red font) and imputed SNPs (in black font). <i>Bottom panel:</i> Pairwise r² values for genotyped SNPs on iCOG array in the 17q21 region covering positions (43.4–44.9 Mb, b.37).</p

Predicted breast and ovarian cancer absolute risks for <i>BRCA1</i> mutation carriers at the 5^th, 10^th, 90^th, and 95^th percentiles of the combined SNP profile distributions.

<p>The minimum, maximum and average risks are also shown. Predicted cancer risks are based on the associations of known breast or ovarian cancer susceptibility loci (identified through GWAS) with cancer risk for <i>BRCA1</i> mutation carriers and loci identified through the present study. Breast cancer risks based on the associations with: 1q32, 10q25.3, 19p13, 6q25.1, 12p11, <i>TOX3</i>, 2q35, <i>LSP1</i>, <i>RAD51L1</i> (based on HR and minor allele frequency estimates from <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen-1003212-t001" target="_blank">Table 1</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen-1003212-t002" target="_blank">Table 2</a>, and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen.1003212.s016" target="_blank">Table S4</a>) and <i>TERT </i><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen.1003212-Bojesen1" target="_blank">[31]</a>. Ovarian cancer risks based on the associations with: 9p22, 8q24, 3q25, 17q21, 19p13 (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen-1003212-t001" target="_blank">Table 1</a>) and 17q21.31, 4q32.3 (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen-1003212-t002" target="_blank">Table 2</a>). Only the top SNP from each region was chosen. Average breast and ovarian cancer risks were obtained from published data <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen.1003212-Antoniou10" target="_blank">[25]</a>. The methods for calculating the predicted risks have been described previously <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen.1003212-Antoniou11" target="_blank">[28]</a>.</p

Associations with SNPs at the novel 17q21 region with ovarian cancer risk for <i>BRCA1</i> and <i>BRCA2</i> mutation carriers.

*<p>HRs estimated under the single disease risk model.</p

Study design for selection of the SNPs and genotyping of <i>BRCA1</i> samples.

<p>GWAS data from 2,727 <i>BRCA1</i> mutation carriers were analysed for associations with breast and ovarian cancer risk and 32,557 SNPs were selected for inclusion on the iCOGS array. A total of 11,705 <i>BRCA1</i> samples (after quality control (QC) checks) were genotyped on the 31,812 <i>BRCA1</i>-GWAS SNPs from the iCOGS array that passed QC. Of these samples, 2,387 had been genotyped at the SNP selection stage and are referred to as “stage 1” samples, whereas 9,318 samples were unique to the iCOGS study (“Stage 2” samples). Next, 17 SNPs that exhibited the most significant associations with breast and ovarian cancer were selected for genotyping in a third stage involving an additional 2,646 <i>BRCA1</i> samples (after QC).</p

Associations with breast or ovarian cancer risk for loci previously reported to be associated with cancer risk for <i>BRCA1</i> mutation carriers.

<p>Freq = frequency of allele 2 in unaffected <i>BRCA1</i> carriers.</p><p>HR = Per allele Hazard Ratio associated with allele 2, under a single disease risk model, unless specified.</p><p>r²: correlation between the SNP in the present study and the published SNP.</p>*<p>SNP not in <i>BRCA1</i> GWAS SNP allocation on iCOGS chip.</p>a<p>: rs13387042 was previously found to be associated only under the 2-df model.</p>b<p>: analysis under a competing risks model.</p

Analysis of associations with breast and ovarian cancer risk simultaneously (competing risks analysis) for SNPs found to be associated with breast or ovarian cancer.

<p>Analysis of associations with breast and ovarian cancer risk simultaneously (competing risks analysis) for SNPs found to be associated with breast or ovarian cancer.</p